Studies will be initiated to define the nature and consequences of the T3-nuclear interaction. Special emphasis will be placed on experiments designed to determine whether or not this interaction does in fact represent the initial step in the series of biochemical reactions which terminate in the expression of hormonal activity at the cellular level. Clinical studies are also planned to define the mechanism underlying the low T3 concentrations observed in patients with nonspecific disease and to assess the physiologic and therapeutic implications of these findings.